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HÆMODIALYSIS IN THE TREATMENT OF GOUT
1209
HÆMODIALYSIS IN THE TREATMENT OF GOUT H. DUNCAN Sydney, M.Sc. Minnesota, M.R.C.P. W. ELLIOTT D. B. HORN M.B. Durh. Ph.D. Edin., F.R.I.C. D. N. S. KERR M.B. Edin., M.Sc. Wisconsin, M.R.C.P., M.R.C.P.E. D. T. PEARSON A. M. ROBSON M.B.
M.B. Durh. M.R.C.P.
M.B. Durh.
Fig. 2-Plantar tophi of case
2.
Departments of Medicine and Pathology (Clinical Chemistry), University of Durham, the Royal Victoria Infirmary, Newcastle upon Tyne, and the Department of Urology, Newcastle General Hospital From the
URIC acid is one of many metabolites removed from patientsvith acute renal failure during hsemodialysis. Direct measurements of the total quantity removed have been made by collecting the dialysis fluid throughout the procedure. Quantities of the order of 1-4 g. were recovered during 4-6 hours’ treatment with the Kolff twin-coil and rotating-coil kidneys (Goldberg et al. 1960, Kennedy et al. 1961). These encouraging results in patients with acute renal failure suggested that hasmodialysis had a potential role in the removal of uric acid from patients with gout. Most gouty patients who have normal, or only mildly impaired, renal function can be treated adequately with uricosuric drugs. We have therefore considered for dialysis only those gouty subjects with renal damage, in whom uricosuric therapy had failed to prevent the Hfrnrrmlattnn nf tnnhi nnii further ciecline in renal 1 fnnl’-
tion.
The pre-
liminary results in two such patients are the subject of this report. The patients brothers and their family tree is illustrated in
are
fig. 1. Case 1 is man
Methods Case 1 was treated on one occasion by haemodialysis, whicl lasted for 11 hours. Case 2 underwent two dialyses at at interval of 4 days. A modified twin-coil kidney (Elliott et a] 1961) was used on each occasion. Heparinised blood-samples were taken at intervals durinj and after dialysis. Dialysis fluid was changed hourly, and an aliquot was taken from each bath, before it was discarded, fo concentration by vacuum distillation and subsequent analysis Urea and uric acid, in blood and concentrated dialysate, werl determined by standard ’Technicon ’ autoanalyser methods. Both patients were kept on low-purine diets during thei: preliminary investigations, and throughout the treatmen period. Plasma-uric-acid level and urinary-uric-acid outpu were both stable during control periods of at least 5 days beforl the first dialysis. Full studies of renal function, uric-acid output on variou regimens, and uric-acid-pool size before treatment were com pared with final results. These will be reported in detail later Results
Patients
year-old
specimens showed no gross abnormality. The patient’s daily output of uric acid was not influenced by uricosuric drugs during observation in hospital.
a
34-
Case1 The plasma-uric-acid levels during dialysis, and the amounts of uric acid removed during each hour of dialysis, are shown in fig. 4. At the beginning of dialysis the plasma-uric-acid was 14.0 mg. per 100 ml. During the lst hour 0-7 g. of uric acid was removed from the patient,
with
gout of 15 years’ duration. A large tophus on the left big toe had been Fig. I-Pedigree of gout in cases 1 and 2. discharging for 6 months, and had failed to heal after surgical curettage. Attacks of joint pain were frequent and protracted, but responded to colchicine and butazolidine. In spite of 4 months’ treatment with uricosuric drugs he continued to accumulate tophi. Renal impairment was shown by a plasma-urea of 210 mg. per 100 ml., but his blood-pressure remained normal at
120/65. Case 2 is a 37-year-old man with tophaceous gout since the age of 18. Tophi had accumulated rapidly over the previous 6 months in spite of uricosuric therapy for over a year and low-purine diet for part of this time. In the few months before
his admission numerous subcutaneous tophi had appeared on both feet (fig. 2). His blood-pressure was 125/65 mm. Hg, but blood-urea was 114 mg. per 100 ml. Needle-biopsy specimens were taken from two sites in the left kidney; one was fixed in formalin, and the other in alcohol (fig. 3). No uric-acid crystals were visible in either specimen; both showed interstitial scarring, tubular atrophy and dilatation, and the presence of albuminous casts. The twenty glomeruli included in the two
Fig. 3-Microscopic appearance of renal biopsy specimen from case 2 showing interstitial fibrosis and tubular casts. (Hmmalum and eosin. x 30.)
1210 Case 2
and the plasma level of uric acid fell to 9-1mg. per 100 ml. A total of 3-5 g. of uric acid was removed during the dialysis, of which 2-5 g.
(73%)
was
Just before the first dialysis the plasma-uric-acid in this patient was 10.8 mg. per 100 ml., and the blood-urea 114 mg. per 100 ml. After 6 hours these levels had fallen to 1.7 and 15 mg. per 100 ml. respectively. 1.8 g. of uric acid was removed during the 6-hour haemodialysis (fig. 5). The second dialysis was performed after an interval of 4 days; on this occasion 2.1 g. of uric acid was removed during 7 hours. After each haemodialysis the plasma-uric-acid rose to predialvsis levels within 4 davs. Discussion Patients with gout have an excess of uric acid in the body, usually due to an increase in the size of the miscible urate pool and often in crystalline form as tophaceous
re-
moved in the first 6 hours. It is obvious that prolonging the procedure beyond the customary 6-7 hours resulted in little extra benefit. After this interval the plasma-uricacid had fallen to low normal levels, and the quantity of uric acid removed per hour was
deposits (Benedict et al. 1949, Geren et al. 1950). Several of the clinical features of gout-tophus formation, joint destruction, and urinary calculus formation-are clearly related to the accumulation of uric acid. The role of uric acid in the genesis of the acute attacks of arthritis is more obscure; but reduction in the total body content of uric acid diminishes the frequency of these attacks, reduces the size of tophi, relieves pain, recalcifies bone, and
correspond-
ingly small. The complications of
Fig. 4-Urea and uric-acid values during heemodialysis of case 1.
haemodialvsis appear to increase with its duration (Hall et al. 1961), and subsequent dialyses have therefore been carried out for shorter periods. After dialysis the plasma-uric-acid rose to 8-5 mg. per 100 ml. in 30 hours and subsequently stabilised at 10.6 mg. per 100 ml. Over the following 2 weeks the discharging tophus healed and the patient has remained free of further attacks for 10 weeks.
improves joint movement (Bartels 1957). Approximately 30-50% of patients with gout are said to die of renal disease (Wyngaarden 1958). Some of these patients have no calculi, and histologically their kidneys show non-specific scarring similar to that found in many forms of chronic renal disease (Sokoloff 1957, Greenbaum et al. 1961). Nevertheless, there are good grounds for believing that the chronic renal failure of gout is caused or aggravated by persistent hyperuricasmia. Acute renal failure is known to complicate the massive release of uric acid during treatment of leukaemia and similar myeloproliferative and neoplastic diseases, which deposits large amounts of uric acid in the parenchyma. Renal function has been restored in such patients after the removal of uric acid by haemodialysis (Firmat et al. 1960). In two patients with gout the plasma non-protein-nitrogen level rose temporarily after a single intravenous injection of urate (Folin et al. 1924). Repeated intravenous injections of smaller amounts of uric acid in laboratory animals eventually cause chronic renal failure (Duncan 1961). Elimination of uric acid from the gouty patient may improve renal function (Phillips 1955, Duncan and Dixon 1960). The mode of action of uric acid on the kidney of the gouty patient may well be the same as that in the laboratory animaldeposition of urate crystals in the tubules, with obstruction, local tubular hydronephrosis, and destruction of the nephron (Smith and Lee 1957, Duncan et al. 1961). Consequently, the standard treatment of gout with hyperuricasmia should include measures designed to reduce the body pool of uric acid. Besides reduced dietary intake of proteins and purines, drugs which increase the renal clearance of uric acid are usually prescribed. These uricosuric drugs are effective in most patients, and their long-continued administration eventually dissolves tophi and restores the plasma-acid level to normal. But they are effective only in patients with reasonably wellpreserved renal function. Once renal failure of moderate degree has appeared, renal clearance of uric acid is further diminished, and tophi accumulate more rapidly, as in our case 2. At this stage of the disease, the total body-urates can be reduced only by palliative surgical curettage of superficial tophi.
Fig. 5-Plasma and urine studies on case 2. D = time ofhaemodialysis. Stippled blocks = uric acid removed
dialysis.
Our
by
was designed to show whether hasmocould remove from patients in this irreversible dialysis of the disease sufficient uric acid to promote the stage
pilot study
1211
resolution of tophi and reduce the plasma-urate level to normal. This would decrease the load on the damaged
kidneys and improve renal function,
or at least prevent its further deterioration. Protracted treatment and observation will be required to answer these questions, but the preliminary results reported here show that haemodialysis has a reasonable chance of success. The capacity of the artificial kidney to remove uric acid from patients with an elevated plasma level had already been established. The questions that had to be answered before these results could be applied to patients with gout
were:
(1) With the lower plasma-urate levels in gout, compared with those in acute renal failure, can an important quantity of uric acid still be removed ? (2) After dialysis, does re-solution of the tophi occur fast enough to raise the plasma-urate level within a few days, and permit repeated hsemodialyses at short intervals ? (3) Does urinary uric-acid excretion fall off so far after dialysis that much of the ground gained is immediately lost ? The answers to these questions suggested by our study far are: (1) With a twin-coil kidney and a reasonable flow-rate 200-400 ml. per min.), about 2 g. of uric acid can be removed so
by a single dialysis of 6-7 hours when the plasma level is about 10.0 mg. per 100 ml. It is evident then that, in gouty patients with expanded miscible-urate pools and tophaceous deposits, repeated dialyses will be required to remove much of the excess body-urate. (2) Hxmodialysis can be repeated (at least at the outset of such therapy) every 3-5 days. Our patients can therefore be treated with the artificial kidney once or twice a week whilst in hospital. (3) After dialysis, the decrease in urinary excretion of uric acid lasted for only 2 days. In the 4 days after dialysis each patient excreted only 100-300 mg. less than on 4 control days before dialysis. This is about 10% of that removed by a single dialysis. ,
The rapid rise in plasma-urate level in the few days after each dialysis is no doubt due partly to redistribution in the urate pool. The part played by re-solution of tophi is currently under investigation. A third source of the urate is purine metabolism. In many gouty patients uric acid is produced by metabolism at a normal rate, but in some there is considerable overproduction (Benedict et al. 1952). This group of patients is probably unsuitable for hxmodialysis, since any advantage gained will be rapidly lost. It would therefore be helpful, before deciding on haemodialysis, to know whether the patient is a fast or slow producer of uric acid; we are currently screening our patients by an isotope-dilution technique with this end in view. The performance of several (perhaps as many as ten) dialyses on each of these patients will present difficulties. It is not feasible to make separate arterial and venous cutdowns each time. Two new approaches to this problem in patients with renal failure have recently been
reported: (1) The use of an indwelling ’Teflon ’ arteriovenous shunt (Quinton et al. 1960). This was attempted in one of our patients, but the shunt became occluded with thrombus within 2- weeks. Though this may have been due to technical faults, it is also possible that such shunts remain patent only when the clotting mechanism is impaired, as in severe renal failure. (2) Repeated percutaneous puncture of femoral artery and vein (Shaldon et al. 1961). This technique has not been used as often as ten times on the same patient, but we intend to explore the possibilities of this method on future subjects.
Summary Two patients with tophaceous gout and impaired renal function were treated with a twin-coil artificial kidney. Relatively large quantities of uric acid were removed from the body during the procedure-about 2 g. in 7 hours. In patients with gout not responding to uricosuric therapy, haemodialysis is the only effective remedy; and in such cases repeated hxmodialyses will probably be
required. We wish to thank Prof. G. A. Smart (under whose care the patients admitted) and Prof. A. L. Latner for help and encouragement; Dr. J. Hart Mercer for reporting on the histological sections; and Sister M. J. 0. Freeman and her staff for provision of low-purine diets. were
REFERENCES
Bartels, E. C. (1957) Metabolism, 6, 297. Benedict, J. D., Forsham, P. H., Stetten, D., Jr. (1949) J. biol. Chem. 181, 183.
Roche, M., Yu, T. F., Bien, E. J., Gutman, A. B., Stetten, D., Jr. (1952) Metabolism, 1, 3. Duncan, H. (1961) Thesis, M.Sc. in Medicine, University of Minnesota, -
U.S.A.
Dixon, A. St. J. (1960) Quart. J. Med. 29, 127. Wakim, K. G., Ward, L. E. (1961) Fed. Proc. 20, 405. Elliott, W., Horn, D. B., Kerr, D. N. S., Pearson, D. T. (1961) Lancet, i, 248. Firmat, J., Vanamee, P., Klauber, L., Krakoff, I., Randall, H. T. (1960) Cancer, 13, 376. Folin, O., Berglund, H., Derick, C. (1924) J. biol. Chem. 60, 361. Geren, W., Bendich, A., Bodansky, O., Brown, G. B. (1950) ibid. 183, 21. Goldberg, M., Castleman, L., Wallace, S. L. (1960) J. Lab. clin. Med. 55, 268. Greenbaum, D., Ross, J. H., Steinberg, V. L. (1961) Brit. med. J. i, 1502. Hall, M., Kerr, D. N. S., Smart, G. A., Ashcroft, R., Elliott, W., Swinney, J. (1961) Brit. J. Urol. 33, 2. Kennedy, A. C., Gray, M. J. B., Dinwoodie, A., Linton, A. L. (1961) Lancet, ii, 996. Phillips, R. W. (1955) Arch. intern. Med. 96, 823. Quinton, W., Dillard, D., Scribner, B. H. (1960) Trans. Amer. Soc. artif. Org, 6, 104. Shaldon, S., Chiandussi, L., Higgs, B. (1961) Lancet, ii, 857. Smith, J. F., Chen, Y. C. (1957) J. exp. Med. 105, 615. Sokoloff, L. (1957) Metabolism, 6, 230. Wyngaarden, J. B. (1958) Arth. Rheum. 1, 191. -
—
LOCAL SARCOID-TISSUE REACTIONS R. ANDERSON M.B. Lond. RESEARCH ASSISTANT
D. GERAINT JAMES M.A., M.D. Cantab., M.R.C.P.
P. M. PETERS M.A., D.M. Oxon.
PHYSICIAN
PATHOLOGIST
ROYAL NORTHERN
HOSPITAL, LONDON, N.7
A. D. THOMSON M.A., M.D. Cantab., M.R.C.P. ASSISTANT PATHOLOGIST BLAND-SUTTON INSTITUTE OF MIDDLESEX
PATHOLOGY, HOSPITAL, LONDON, W.1
"
SARCOIDOSIS is a systemic granulomatous disease of undetermined aetiology and pathogenesis. Mediastinal and
peripheral lymph nodes, lungs, liver, spleen, skin, eyes, phalangeal bones and parotid glands are most often involved, but other organs
or
tissues may be affected. The Kveim test is
frequently positive and the tuberculin reaction often negative. Other common findings are hypercalciuria and increased serum globulin levels. The histological appearance of epithelioid tubercles with inconspicuous necrosis is not pathognomonic; tuberculosis, fungal infection, beryllium disease and local sarcoid-tissue reactions must be excluded. The diagnosis comprises consistent clinical and/or radiological features together with histological confirmation by biopsy or by a positive Kveim test." The above is
a descriptive definition of the disease agreed by participants in an International Conference on Sarcoidosis held in June, 1960, in Washington, D.C. The
upon
purpose of this paper is to draw attention to those local
sarcoid-tissue or granulomatous reactions which continue be confused with sarcoidosis, and so to underline the doctrine that the finding of sarcoid tissue does not necessarily imply that the patient has sarcoidosis.
to
HÆMODIALYSIS IN THE TREATMENT OF GOUT H. DUNCAN Sydney, M.Sc. Minnesota, M.R.C.P. W. ELLIOTT D. B. HORN M.B. Durh. Ph.D. Edin., F.R.I.C. D. N. S. KERR M.B. Edin., M.Sc. Wisconsin, M.R.C.P., M.R.C.P.E. D. T. PEARSON A. M. ROBSON M.B.
M.B. Durh. M.R.C.P.
M.B. Durh.
Fig. 2-Plantar tophi of case
2.
Departments of Medicine and Pathology (Clinical Chemistry), University of Durham, the Royal Victoria Infirmary, Newcastle upon Tyne, and the Department of Urology, Newcastle General Hospital From the
URIC acid is one of many metabolites removed from patientsvith acute renal failure during hsemodialysis. Direct measurements of the total quantity removed have been made by collecting the dialysis fluid throughout the procedure. Quantities of the order of 1-4 g. were recovered during 4-6 hours’ treatment with the Kolff twin-coil and rotating-coil kidneys (Goldberg et al. 1960, Kennedy et al. 1961). These encouraging results in patients with acute renal failure suggested that hasmodialysis had a potential role in the removal of uric acid from patients with gout. Most gouty patients who have normal, or only mildly impaired, renal function can be treated adequately with uricosuric drugs. We have therefore considered for dialysis only those gouty subjects with renal damage, in whom uricosuric therapy had failed to prevent the Hfrnrrmlattnn nf tnnhi nnii further ciecline in renal 1 fnnl’-
tion.
The pre-
liminary results in two such patients are the subject of this report. The patients brothers and their family tree is illustrated in
are
fig. 1. Case 1 is man
Methods Case 1 was treated on one occasion by haemodialysis, whicl lasted for 11 hours. Case 2 underwent two dialyses at at interval of 4 days. A modified twin-coil kidney (Elliott et a] 1961) was used on each occasion. Heparinised blood-samples were taken at intervals durinj and after dialysis. Dialysis fluid was changed hourly, and an aliquot was taken from each bath, before it was discarded, fo concentration by vacuum distillation and subsequent analysis Urea and uric acid, in blood and concentrated dialysate, werl determined by standard ’Technicon ’ autoanalyser methods. Both patients were kept on low-purine diets during thei: preliminary investigations, and throughout the treatmen period. Plasma-uric-acid level and urinary-uric-acid outpu were both stable during control periods of at least 5 days beforl the first dialysis. Full studies of renal function, uric-acid output on variou regimens, and uric-acid-pool size before treatment were com pared with final results. These will be reported in detail later Results
Patients
year-old
specimens showed no gross abnormality. The patient’s daily output of uric acid was not influenced by uricosuric drugs during observation in hospital.
a
34-
Case1 The plasma-uric-acid levels during dialysis, and the amounts of uric acid removed during each hour of dialysis, are shown in fig. 4. At the beginning of dialysis the plasma-uric-acid was 14.0 mg. per 100 ml. During the lst hour 0-7 g. of uric acid was removed from the patient,
with
gout of 15 years’ duration. A large tophus on the left big toe had been Fig. I-Pedigree of gout in cases 1 and 2. discharging for 6 months, and had failed to heal after surgical curettage. Attacks of joint pain were frequent and protracted, but responded to colchicine and butazolidine. In spite of 4 months’ treatment with uricosuric drugs he continued to accumulate tophi. Renal impairment was shown by a plasma-urea of 210 mg. per 100 ml., but his blood-pressure remained normal at
120/65. Case 2 is a 37-year-old man with tophaceous gout since the age of 18. Tophi had accumulated rapidly over the previous 6 months in spite of uricosuric therapy for over a year and low-purine diet for part of this time. In the few months before
his admission numerous subcutaneous tophi had appeared on both feet (fig. 2). His blood-pressure was 125/65 mm. Hg, but blood-urea was 114 mg. per 100 ml. Needle-biopsy specimens were taken from two sites in the left kidney; one was fixed in formalin, and the other in alcohol (fig. 3). No uric-acid crystals were visible in either specimen; both showed interstitial scarring, tubular atrophy and dilatation, and the presence of albuminous casts. The twenty glomeruli included in the two
Fig. 3-Microscopic appearance of renal biopsy specimen from case 2 showing interstitial fibrosis and tubular casts. (Hmmalum and eosin. x 30.)
1210 Case 2
and the plasma level of uric acid fell to 9-1mg. per 100 ml. A total of 3-5 g. of uric acid was removed during the dialysis, of which 2-5 g.
(73%)
was
Just before the first dialysis the plasma-uric-acid in this patient was 10.8 mg. per 100 ml., and the blood-urea 114 mg. per 100 ml. After 6 hours these levels had fallen to 1.7 and 15 mg. per 100 ml. respectively. 1.8 g. of uric acid was removed during the 6-hour haemodialysis (fig. 5). The second dialysis was performed after an interval of 4 days; on this occasion 2.1 g. of uric acid was removed during 7 hours. After each haemodialysis the plasma-uric-acid rose to predialvsis levels within 4 davs. Discussion Patients with gout have an excess of uric acid in the body, usually due to an increase in the size of the miscible urate pool and often in crystalline form as tophaceous
re-
moved in the first 6 hours. It is obvious that prolonging the procedure beyond the customary 6-7 hours resulted in little extra benefit. After this interval the plasma-uricacid had fallen to low normal levels, and the quantity of uric acid removed per hour was
deposits (Benedict et al. 1949, Geren et al. 1950). Several of the clinical features of gout-tophus formation, joint destruction, and urinary calculus formation-are clearly related to the accumulation of uric acid. The role of uric acid in the genesis of the acute attacks of arthritis is more obscure; but reduction in the total body content of uric acid diminishes the frequency of these attacks, reduces the size of tophi, relieves pain, recalcifies bone, and
correspond-
ingly small. The complications of
Fig. 4-Urea and uric-acid values during heemodialysis of case 1.
haemodialvsis appear to increase with its duration (Hall et al. 1961), and subsequent dialyses have therefore been carried out for shorter periods. After dialysis the plasma-uric-acid rose to 8-5 mg. per 100 ml. in 30 hours and subsequently stabilised at 10.6 mg. per 100 ml. Over the following 2 weeks the discharging tophus healed and the patient has remained free of further attacks for 10 weeks.
improves joint movement (Bartels 1957). Approximately 30-50% of patients with gout are said to die of renal disease (Wyngaarden 1958). Some of these patients have no calculi, and histologically their kidneys show non-specific scarring similar to that found in many forms of chronic renal disease (Sokoloff 1957, Greenbaum et al. 1961). Nevertheless, there are good grounds for believing that the chronic renal failure of gout is caused or aggravated by persistent hyperuricasmia. Acute renal failure is known to complicate the massive release of uric acid during treatment of leukaemia and similar myeloproliferative and neoplastic diseases, which deposits large amounts of uric acid in the parenchyma. Renal function has been restored in such patients after the removal of uric acid by haemodialysis (Firmat et al. 1960). In two patients with gout the plasma non-protein-nitrogen level rose temporarily after a single intravenous injection of urate (Folin et al. 1924). Repeated intravenous injections of smaller amounts of uric acid in laboratory animals eventually cause chronic renal failure (Duncan 1961). Elimination of uric acid from the gouty patient may improve renal function (Phillips 1955, Duncan and Dixon 1960). The mode of action of uric acid on the kidney of the gouty patient may well be the same as that in the laboratory animaldeposition of urate crystals in the tubules, with obstruction, local tubular hydronephrosis, and destruction of the nephron (Smith and Lee 1957, Duncan et al. 1961). Consequently, the standard treatment of gout with hyperuricasmia should include measures designed to reduce the body pool of uric acid. Besides reduced dietary intake of proteins and purines, drugs which increase the renal clearance of uric acid are usually prescribed. These uricosuric drugs are effective in most patients, and their long-continued administration eventually dissolves tophi and restores the plasma-acid level to normal. But they are effective only in patients with reasonably wellpreserved renal function. Once renal failure of moderate degree has appeared, renal clearance of uric acid is further diminished, and tophi accumulate more rapidly, as in our case 2. At this stage of the disease, the total body-urates can be reduced only by palliative surgical curettage of superficial tophi.
Fig. 5-Plasma and urine studies on case 2. D = time ofhaemodialysis. Stippled blocks = uric acid removed
dialysis.
Our
by
was designed to show whether hasmocould remove from patients in this irreversible dialysis of the disease sufficient uric acid to promote the stage
pilot study
1211
resolution of tophi and reduce the plasma-urate level to normal. This would decrease the load on the damaged
kidneys and improve renal function,
or at least prevent its further deterioration. Protracted treatment and observation will be required to answer these questions, but the preliminary results reported here show that haemodialysis has a reasonable chance of success. The capacity of the artificial kidney to remove uric acid from patients with an elevated plasma level had already been established. The questions that had to be answered before these results could be applied to patients with gout
were:
(1) With the lower plasma-urate levels in gout, compared with those in acute renal failure, can an important quantity of uric acid still be removed ? (2) After dialysis, does re-solution of the tophi occur fast enough to raise the plasma-urate level within a few days, and permit repeated hsemodialyses at short intervals ? (3) Does urinary uric-acid excretion fall off so far after dialysis that much of the ground gained is immediately lost ? The answers to these questions suggested by our study far are: (1) With a twin-coil kidney and a reasonable flow-rate 200-400 ml. per min.), about 2 g. of uric acid can be removed so
by a single dialysis of 6-7 hours when the plasma level is about 10.0 mg. per 100 ml. It is evident then that, in gouty patients with expanded miscible-urate pools and tophaceous deposits, repeated dialyses will be required to remove much of the excess body-urate. (2) Hxmodialysis can be repeated (at least at the outset of such therapy) every 3-5 days. Our patients can therefore be treated with the artificial kidney once or twice a week whilst in hospital. (3) After dialysis, the decrease in urinary excretion of uric acid lasted for only 2 days. In the 4 days after dialysis each patient excreted only 100-300 mg. less than on 4 control days before dialysis. This is about 10% of that removed by a single dialysis. ,
The rapid rise in plasma-urate level in the few days after each dialysis is no doubt due partly to redistribution in the urate pool. The part played by re-solution of tophi is currently under investigation. A third source of the urate is purine metabolism. In many gouty patients uric acid is produced by metabolism at a normal rate, but in some there is considerable overproduction (Benedict et al. 1952). This group of patients is probably unsuitable for hxmodialysis, since any advantage gained will be rapidly lost. It would therefore be helpful, before deciding on haemodialysis, to know whether the patient is a fast or slow producer of uric acid; we are currently screening our patients by an isotope-dilution technique with this end in view. The performance of several (perhaps as many as ten) dialyses on each of these patients will present difficulties. It is not feasible to make separate arterial and venous cutdowns each time. Two new approaches to this problem in patients with renal failure have recently been
reported: (1) The use of an indwelling ’Teflon ’ arteriovenous shunt (Quinton et al. 1960). This was attempted in one of our patients, but the shunt became occluded with thrombus within 2- weeks. Though this may have been due to technical faults, it is also possible that such shunts remain patent only when the clotting mechanism is impaired, as in severe renal failure. (2) Repeated percutaneous puncture of femoral artery and vein (Shaldon et al. 1961). This technique has not been used as often as ten times on the same patient, but we intend to explore the possibilities of this method on future subjects.
Summary Two patients with tophaceous gout and impaired renal function were treated with a twin-coil artificial kidney. Relatively large quantities of uric acid were removed from the body during the procedure-about 2 g. in 7 hours. In patients with gout not responding to uricosuric therapy, haemodialysis is the only effective remedy; and in such cases repeated hxmodialyses will probably be
required. We wish to thank Prof. G. A. Smart (under whose care the patients admitted) and Prof. A. L. Latner for help and encouragement; Dr. J. Hart Mercer for reporting on the histological sections; and Sister M. J. 0. Freeman and her staff for provision of low-purine diets. were
REFERENCES
Bartels, E. C. (1957) Metabolism, 6, 297. Benedict, J. D., Forsham, P. H., Stetten, D., Jr. (1949) J. biol. Chem. 181, 183.
Roche, M., Yu, T. F., Bien, E. J., Gutman, A. B., Stetten, D., Jr. (1952) Metabolism, 1, 3. Duncan, H. (1961) Thesis, M.Sc. in Medicine, University of Minnesota, -
U.S.A.
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LOCAL SARCOID-TISSUE REACTIONS R. ANDERSON M.B. Lond. RESEARCH ASSISTANT
D. GERAINT JAMES M.A., M.D. Cantab., M.R.C.P.
P. M. PETERS M.A., D.M. Oxon.
PHYSICIAN
PATHOLOGIST
ROYAL NORTHERN
HOSPITAL, LONDON, N.7
A. D. THOMSON M.A., M.D. Cantab., M.R.C.P. ASSISTANT PATHOLOGIST BLAND-SUTTON INSTITUTE OF MIDDLESEX
PATHOLOGY, HOSPITAL, LONDON, W.1
"
SARCOIDOSIS is a systemic granulomatous disease of undetermined aetiology and pathogenesis. Mediastinal and
peripheral lymph nodes, lungs, liver, spleen, skin, eyes, phalangeal bones and parotid glands are most often involved, but other organs
or
tissues may be affected. The Kveim test is
frequently positive and the tuberculin reaction often negative. Other common findings are hypercalciuria and increased serum globulin levels. The histological appearance of epithelioid tubercles with inconspicuous necrosis is not pathognomonic; tuberculosis, fungal infection, beryllium disease and local sarcoid-tissue reactions must be excluded. The diagnosis comprises consistent clinical and/or radiological features together with histological confirmation by biopsy or by a positive Kveim test." The above is
a descriptive definition of the disease agreed by participants in an International Conference on Sarcoidosis held in June, 1960, in Washington, D.C. The
upon
purpose of this paper is to draw attention to those local
sarcoid-tissue or granulomatous reactions which continue be confused with sarcoidosis, and so to underline the doctrine that the finding of sarcoid tissue does not necessarily imply that the patient has sarcoidosis.
to